This is a competitive renewal application to continue to explore marine microorganisms as a new source for antitumor-antibiotics. The project continues as a collaboration between chemists and microbiologists at the Scripps Institution of Oceanography in La Jolla, CA. and cancer biologists at the Bristol-Myers Squibb Pharmaceutical Research Institute in Princeton, NJ. Studies proposed for the renewal period include the following: The isolation, cultivation and biological evaluation of marine microorganisms from previously unstudied groups, including gliding bacteria, the zoosporic (lower) fungi, and other unusual classes. In excess of 5,000 strains will be investigated during this renewal period. To continue to chemically-define new molecules which show in vitro activity toward selected cancer relevant targets such as IGF-1, cdk, Ras, PC3, and VEGFR-2, topoisomerase I and II and tubulin-based bioassays. To produce in large scale 5 newly discovered classes of in vitro antitumor agents for in vivo assays including the leukemia models P388 and L1210, and the murine solid tumor models M109 and M50766. To continue to develop a long-term database describing the unique distributions, culture requirements, and metabolic products produced by marine microorganisms isolated from selected habitats. To continue to construct a large marine microorganism culture collection, maintained at - 100 degrees Celsius, which focuses on unique organisms we have been able to cultivate. The collection will grow with respect to the new fungi and gliding bacteria we will add during this project period.